The disabling effects of chronic cerebral insult and neuropsychiatric disorders were evaluated by a broad range of neuropsychological tests evaluating brain-behavior relations in man. Asymptomatic long-term survivors of acute lymphoblastic leukemia (ALL) who received CNS preventive therapy (cranial irradiation and intrathecal chemotherapy) were studied. Based on CT scan findings, the patients were divided into three groups: normal scans, cortical atrophy; intracerebral calcifications. Memory and learning were significantly impaired in children with abnormal scans, more so for the patients with calcification. In addition, all patients with abnormal CT scans showed significant attentional dysfunctions. Adolescents with obsessive compulsive features exhibited a cluster of neuropsychological deficits which correlated with ventricular enlargement. Deficits were identified in spatial judgement and spatial learning. It was suggested that an imbalance in the inhibitory functions of the frontal lobe and limbic systems may contribute to obsessive compulsive behavior. Patients with Tourette's Syndrome were evaluated in an effort to characterize the neuropsychological defects in frontal inhibitory mechanisms. Positron emission tomographic (PET) data of regional cerebral activity from these patients will be correlated with test performance.